Abstract

While highly active anti-retroviral therapy (HAART) can suppress HIV-1 replication, treatment currently does not eradicate infection or prevent a low level of continued replication. The major objective of this project is directed to defining the anatomic and cellular compartments in which HIV-1 is produced and persists before and during HAART, and from which infection re-emerges on discontinuation of HAART.
The Specific Aim of the project is to identify, characterize and quantify cellular sources of virus production and persistence in gutassociated lymphatic tissues (GALT) and peripheral lymphatic tissues (LTs), using state-of-the-art in situ Technologies of in situ hybridization, in situ PCR, immunohistochemistry and quantitative image analysis, with the long-term goal of capitalizing on the new insights into HIV-1 reservoirs generated by this analysis to design even more effective treatments.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI074340-04
Application #
8316364
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
4
Fiscal Year
2011
Total Cost
$304,770
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Kityo, Cissy; Makamdop, Krystelle Nganou; Rothenberger, Meghan et al. (2018) Lymphoid tissue fibrosis is associated with impaired vaccine responses. J Clin Invest 128:2763-2773
Estes, Jacob D; Kityo, Cissy; Ssali, Francis et al. (2017) Defining total-body AIDS-virus burden with implications for curative strategies. Nat Med 23:1271-1276
Cory, Theodore J; He, Hui; Winchester, Lee C et al. (2016) Alterations in P-Glycoprotein Expression and Function Between Macrophage Subsets. Pharm Res 33:2713-21
Lorenzo-Redondo, Ramon; Fryer, Helen R; Bedford, Trevor et al. (2016) Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature 530:51-56
Sanchez, Joyce L; Hunt, Peter W; Reilly, Cavan S et al. (2015) Lymphoid fibrosis occurs in long-term nonprogressors and persists with antiretroviral therapy but may be reversible with curative interventions. J Infect Dis 211:1068-75
Cory, Theodore J; Winchester, Lee C; Robbins, Brian L et al. (2015) A rapid spin through oil results in higher cell-associated concentrations of antiretrovirals compared with conventional cell washing. Bioanalysis 7:1447-55
Winchester, Lee C; Podany, Anthony T; Baldwin, Joshua S et al. (2015) Determination of the rifamycin antibiotics rifabutin, rifampin, rifapentine and their major metabolites in human plasma via simultaneous extraction coupled with LC/MS/MS. J Pharm Biomed Anal 104:55-61
Mitchell, Caroline; Roemer, Emily; Nkwopara, Evangelyn et al. (2014) Correlation between plasma, intracellular, and cervical tissue levels of raltegravir at steady-state dosing in healthy women. Antimicrob Agents Chemother 58:3360-5
Fletcher, Courtney V; Staskus, Kathryn; Wietgrefe, Stephen W et al. (2014) Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A 111:2307-12
Misemer, Benjamin S; Skubitz, Amy P N; Carlos Manivel, J et al. (2014) Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity. Cancer Med 3:81-90

Showing the most recent 10 out of 30 publications